Everolimus Approved as Adjunctive Treatment for Tuberous Sclerosis-Associated Partial-Onset Seizures
The Food and Drug Administration (FDA) has granted approval for the use of everolimus (Afinitor DISPERZ; Novartis, East Hanover, NJ) to treat tuberous sclerosis complex (TSC)-associated partial onset seizures for patients aged 2 years and older. This is the first approved adjunctive treatment for TSC-associated seizures, which become nonresponsive to available antiepileptic therapies in more that 60% of patients with TSC-associated seizures.
Approval for the treatment of TSC-associated seizures was based on efficacy and safety data from the pivotal phase 3 EXIST-3 study that showed that adjunctive therapy with everolimus significantly reduced seizure frequency in patients with treatment-resistant TSC-associated seizures compared to those treated with a placebo. Treatment with everolimus at one of two doses reduced seizure frequency by a median rate of 29.3% (lower dose; P = .003) and 39.6% (higher dose; P = .001) versus a 14.9% reduction in seizure frequency with placebo.
Everolimus is available as tablets for oral suspension and is also indicated for treatment of patients with TSC-associated noncancerous brain tumors (subependymal giant cell astrocytoma [SEGA]) and TSC-associated kidney tumors. The most common all-grade adverse events of any cause included stomatitis, diarrhea, nasopharyngitis, upper respiratory tract infection, and pyrexia.
Everolimus inhibits rapamycin, which has been shown to be overactive in animal models of TSC causing neuronal dysplasia, aberrant axonogenesis, increased synaptic currents, reduced myelination, and disruption of the cortical laminar structure that lead to neurodevelopmental abnormalities.
"We are pleased that this latest approval for Afinitor DISPERZ in the US will make an important difference to patients with tuberous sclerosis complex who experience partial-onset seizures, one of the most debilitating manifestations of TSC," said Ameet Mallik, Executive Vice President, Novartis Oncology US. "This is a welcome advance that reinforces the commitment of Novartis to patients with rare diseases."